Abstract

Spinocerebellar Ataxia type 7 (SCA7, OMIM # 164500) is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive cerebellar ataxia and blindness. SCA7 is part of the large family of autosomal dominant cerebellar ataxias (ADCAs), and was estimated to account for 1–11.7% of ADCAs in diverse populations. The frequency of SCA7 is higher where local founder effects were observed as in Scandinavia, Korea, South Africa and Mexico. SCA7 is pathomechanistically related to the group of CAG/polyglutamine (polyQ) expansion disorders, which includes other SCAs (1–3, 6 and 17), Huntington’s disease, spinal bulbar muscular atrophy and dentatorubro pallidoluysian atrophy. Two distinctive characteristics of SCA7 are the strong anticipation by which earlier onset and more severe symptoms are observed in successive generations of affected families, and the loss of visual acuity due to cone-rod dystrophy of the retina. The pathology is caused by an unstable CAG repeat expansion coding for a polyQ stretch in Ataxin-7 (ATXN7). PolyQ expansion in ATXN7 confers toxic properties and leads to selective neuronal degeneration in the cerebellum, the brain stem and the retina. Herein, we summarize the genetic, clinical and pathological features of SCA7 and review our current knowledge of pathomechanisms and preclinical studies.

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Acknowledgements

We are grateful to Nathalie Daigle for critical reading of the manuscript. YT was supported by funding from Institut National de la Santé et de la Recherche Médicale (INSERM); Centre National de la Recherche Scientifique (CNRS); University of Strasbourg; Retina-France (YT); ANR-10-LABX-0030-INRT from the French state fund through the Agence Nationale de la Recherche (ANR) under the frame programme Investissements d’Avenir ANR-10-IDEX-0002-02; the ANR-Ciliataxia N° ANR-13-BSV1-0016-01; the Fondation pour la recherche médicale (FRM DVS20131228917). AK was supported by fellowships from the fundation Connaître les Syndrômes Cérébelleux (CSC).

Conflict of Interest Statement The authors declare no conflict of interest.